SARS-CoV-2-host proteome interactions for antiviral drug discovery.

Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP-MS) and the complementary proximity-based labeling MS method (BioID-MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS-CoV-2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image-based drug screen with infectious SARS-CoV-2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein-protein interactions.

Liu X ，Huuskonen S ，Laitinen T ，Redchuk T ，Bogacheva M ，Salokas K ，Pöhner I ，Öhman T ，Tonduru AK ，Hassinen A ，Gawriyski L ，Keskitalo S ，Vartiainen MK ，Pietiäinen V ，Poso A ，Varjosalo M ... -  《Molecular Systems Biology》

Mapping the SARS-CoV-2-Host Protein-Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics.

Terracciano R ，Preianò M ，Fregola A ，Pelaia C ，Montalcini T ，Savino R ... -  《-》

Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy.

Alonzi T ，Aiello A ，Petrone L ，Najafi Fard S ，D'Eletto M ，Falasca L ，Nardacci R ，Rossin F ，Delogu G ，Castilletti C ，Capobianchi MR ，Ippolito G ，Piacentini M ，Goletti D ... -  《Cells》

Open Science Resources for the Mass Spectrometry-Based Analysis of SARS-CoV-2.

Bittremieux W ，Adams C ，Laukens K ，Dorrestein PC ，Bandeira N ... -  《-》

Cellular host factors for SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives and caused a global economic crisis. No effective antiviral drugs are currently available to treat infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The medical need imposed by the pandemic has spurred unprecedented research efforts to study coronavirus biology. Every virus depends on cellular host factors and pathways for successful replication. These proviral host factors represent attractive targets for antiviral therapy as they are genetically more stable than viral targets and may be shared among related viruses. The application of various 'omics' technologies has led to the rapid discovery of proviral host factors that are required for the completion of the SARS-CoV-2 life cycle. In this Review, we summarize insights into the proviral host factors that are required for SARS-CoV-2 infection that were mainly obtained using functional genetic and interactome screens. We discuss cellular processes that are important for the SARS-CoV-2 life cycle, as well as parallels with non-coronaviruses. Finally, we highlight host factors that could be targeted by clinically approved molecules and molecules in clinical trials as potential antiviral therapies for COVID-19.

Baggen J ，Vanstreels E ，Jansen S ，Daelemans D ... -  《-》